Multi-System Analysis of Opioid Receptor Binding

NCT05528848 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 851051
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study will enroll up to 60 adults (including 30 females and 30 males) in three cohorts of up to 20 subjects each. In all three groups, \[11C\]carfentanil whole-body PET imaging will be used to examine the central nervous system (CNS) and broader systemic opioid binding in an initial scan session. In the two groups not receiving standard of care medication assisted treatment (MAT) for opioid use disorder (OUD) the effects on \[11C\]carfentanil binding potential of the blockade of opioid binding by the non-selective opioid antagonist naloxone administered parenterally in a second scan session will also be examined. If two scans are completed they can be done on the same day or on different days.

Conditions

Healthy; Opioid Use Disorder

Keywords

Medication Assisted Treatment; Buprenorphine; Naloxone

Outcome Measures

Primary Outcomes (2)

• MOR BPND measurement - [11C]carfentanil

  Measure MOR BPND following the administration of \[11C\]carfentanil alone in 5 brain regions of interest (ROIs) relevant to addiction (the subgenual anterior cingulate, ventral pallidum, amygdala, nucleus accumbens, and dorsal striatum), spinal cord (key role in transmitting pain signals) and organs outside the central nervous system (CNS) that contain mu-opioid receptors (e.g., the gastrointestinal tract, heart).

  Baseline

• MOR BPND measurement - naloxone and [11C]carfentanil

  Measure MOR BPND following the administration of both naloxone and \[11C\]carfentanil in 5 brain regions of interest (ROIs) relevant to addiction (the subgenual anterior cingulate, ventral pallidum, amygdala, nucleus accumbens, and dorsal striatum), spinal cord (key role in transmitting pain signals) and organs outside the central nervous system (CNS) that contain mu-opioid receptors (e.g., the gastrointestinal tract, heart).

  Follow up - 1 day to 6 weeks

Secondary Outcomes (1)

• MOR BPND measurement - loperamide and [11C]carfentanil

  Follow up - 1 day to 6 weeks

Study Arms (3)

Opioid Use Disorder and Medication Assisted Treatment (OUD+/MAT-)

EXPERIMENTAL

Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the first study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the second study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the second scan session and there will be a break between the two scan sessions of approximately 3 hours.

Drug: Carfentanil, C-11; Drug: Naloxone

Opioid Use Disorder Only (OUD+/MAT-)

EXPERIMENTAL

Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the first study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the second study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the second scan session and there will be a break between the two scan sessions of approximately 3 hours.

Drug: Carfentanil, C-11; Drug: Naloxone

Healthy Controls (OUD-)

EXPERIMENTAL

Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the 1st study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the 2nd study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the 2nd scan and there will be a break between the two scans of approximately 3 hours. For the optional 3rd study scan 4 mg capsule or 30 mL solution standard adult dose of loperamide hydrochloride will be given orally 45-75 minutes prior to the\[11C\]carfentanil injection.

Drug: Carfentanil, C-11; Drug: Naloxone; Drug: Loperamide Hydrochloride

Interventions

Carfentanil, C-11 DRUG

Investigational radiotracer to be injected by IV as s a bolus during both study PET/CT scans.

Also known as: [11C]Carfentanil

Healthy Controls (OUD-); Opioid Use Disorder Only (OUD+/MAT-); Opioid Use Disorder and Medication Assisted Treatment (OUD+/MAT-)

Naloxone DRUG

Non-selective opioid antagonist injected by IV parenterally during the second study PET/CT scan only.

Healthy Controls (OUD-); Opioid Use Disorder Only (OUD+/MAT-); Opioid Use Disorder and Medication Assisted Treatment (OUD+/MAT-)

Loperamide Hydrochloride DRUG

Loperamide is an FDA- approved, over-the-counter drug for the control and symptomatic relief of acute or chronic diarrhea given orally prior to the optional HC third PET/CT scan only.

Also known as: Imodium

Healthy Controls (OUD-)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Cohort 1 (OUD+/MAT+):
• years of age
• Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.
• Fluent in English and able to provide written informed consent in English.
• OUD positive (+): Participants will meet DSM-5 criteria for a lifetime diagnosis of OUD and will be on a stable dosage of buprenorphine or methadone treatment for at least four weeks prior to the screening visit.
• Cohort 2 (OUD+/MAT-):
• years of age
• Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.
• Fluent in English and able to provide written informed consent in English.
• OUD positive (+): Participants will meet DSM-5 criteria for a lifetime diagnosis of OUD, but cannot meet criteria for OUD in the 2 months prior to screening, has not used an opioid for any reason in the 30 days prior to screening as evidenced by self-report, medical record review, and urine drug testing at screening and and on the day of the PET scan, and has not received MAT for OUD during the 12 months prior to screening.
• Cohort 3 (OUD-, Healthy Controls):
• Healthy males and females, 18-50 years of age
• Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.
• Fluent in English and able to provide written informed consent in English.
• OUD negative (-): Must never have met criteria for OUD (as per DSM-5) and cannot have used an opioid for any reason in the past 30 days prior to screening as evidenced by self-report, medical record review, and urine drug testing at screening.

You may not qualify if:

• Cohort 1 (OUD+/MAT+):
• Women who are pregnant or breast feeding will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening and on the day of each of the PET/CT scans.
• Subjects who report claustrophobia, which in the opinion of an investigator would interfere with acquisition of the structural MRI required for PET co-registration, and/or the PET scan itself.
• Contraindications to MRI (e.g., metal in the body that cannot be removed and is not MRI compatible). An MRI screening form will be completed during screening.
• Current major DSM-5 Axis 1 psychiatric diagnosis that requires treatment with a medication that interferes with opioid receptor binding, as identified during psychiatric interview or mental status examination at screening/baseline.
• History of epilepsy or seizure disorder, head trauma or brain (CNS) tumor as assessed by medical record review and/or self-report
• Current severe substance use disorder (SUD), other than OUD or, cannabis use disorder, with self-reported heavy drug use in the past 3 months and a positive urine toxicology screen for that drug (may be repeated once), and /or current pharmacological treatment for an SUD other than OUD that would interfere with study procedures and outcome.
• A breath alcohol concentration (BAC) reading \> 0.01 or a urine toxicology test positive for prohibited drugs.
• Allergic reaction to any opioid or naloxone
• Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
• Any current medical condition, illness, or disorder as assessed by medical record review and/or self-report that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study or interfere with distribution of the radiotracer.
• Cohort 2 (OUD+/MAT-):
• Women who are pregnant or breast feeding are not eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening and on the day of each of the PET/CT scans.
• Subjects who report claustrophobia, which in the opinion of an investigator would interfere with acquisition of the structural MRI required for PET co-registration, and/or the PET scan itself.
• Contraindications to MRI (e.g., metal in the body that cannot be removed and is not MRI compatible). An MRI screening form will be completed during screening.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania, Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

carfentanil; 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); Naloxone; Loperamide

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

3-Hydroxysteroid Dehydrogenases; Hydroxysteroid Dehydrogenases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2022
• First Posted: September 6, 2022
• Study Start: September 20, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

US (1)